Purpose: To evaluate the rate of corneal swelling induced by hypoosmolar riboflavin in patients with progressive keratoconus (KCN) with corneal thickness <400 <mu>m after the induction phase using riboflavin with 20% dextran during epithelium-off corneal crosslinking (CXL). Methods: Prospective, nonrandomized, single-center consecutive case series. Preoperative assessments included tomography, specular microscopy, and hysteresis. After epithelial debridement, riboflavin with 20% dextran (Photrexa Viscous; Glaukos, Burlington, MA) was applied at 2-min intervals during a 30-min induction phase. Eyes that dehydrated to a minimum corneal thickness (MCT) of <400 <mu>m after induction (postinduction pachymetry) were recruited. Hypoosmolar riboflavin 0.146% (Photrexa; Glaukos) was used every 10 s to induce stromal swelling, with pachymetry performed every 30 s until the MCT was >= 400 mu m (postswelling pachymetry). Corneal swelling rate was compared with variables using regression analysis. Results: In 31 eyes of 31 patients, mean postinduction pachymetry was 338.4 +/- 28.7 mu m. Hypoosmolar riboflavin induced a postswelling pachymetry of 413.4 +/- 15.0 mu m over a mean of 5.2 +/- 3.2 min, and the average stromal swelling rate was 10.3 +/- 8.7 mu m/30 s. All eyes reached a postswelling pachymetry MCT >= 400 mu m and no cases were aborted. Eyes with highly severe KCN (Kmax >70 and Belin/Ambrosio enhanced ectasia display final D score >17) experienced quicker swelling (14.4 +/- 12.8 mu m/30 s and 14.9 +/- 12.4 mu m/30 s, respectively; P < 0.05 for both). A thicker postinduction pachymetry was moderately associated with a faster rate of swelling (rs = 0.389; P = 0.030). Conclusions: Hypoosmolar riboflavin 0.146% can be safely employed in thinner corneas, allowing for swelling to >= 400 <mu>m for epithelium-off CXL. Associations between swelling rate, KCN severity, and postinduction pachymetry were determined, allowing for a more accurate prediction of procedure time during CXL.